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Gene rearrangements...
Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing
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- Jiao, Xiang (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Molecular Cancer Genetics
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- Hooper, Sean D. (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Djureinovic, Tatjana (författare)
- Uppsala universitet,Genomik
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- Larsson, Chatarina (författare)
- Uppsala universitet,Genomik
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- Wärnberg, Fredrik (författare)
- Uppsala universitet,Endokrinkirurgi
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- Tellgren-Roth, Christian (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Botling, Johan (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
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- Sjöblom, Tobias (författare)
- Uppsala universitet,Genomik
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(creator_code:org_t)
- 2013-03-12
- 2013
- Engelska.
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://bmcgenomics....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results: We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions: Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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